•Non-puerperal uterine inversion can be associated with uterine sarcomas.•Adenosarcoma is a tumor composed of benign epithelium and malignant stroma.•If malignancy is suspected or confirmed treatment of uterine inversion with hysterectomy is advised.

A 40-year-old female patient presented to a secondary facility with dull lower abdominal pain and a persistent low-grade fever. Her laboratory results showed elevated inflammation markers. A CT scan revealed two abscesses in the lesser pelvic region in direct contact with the apex of the appendix, the posterior wall of the uterus, and the right-side appendages. The patient responded well to intravenous antibiotics, and an MRI scan revealed the cause to be an appendiceal rupture. The patient was scheduled for an appendectomy. The procedure started laparoscopically but had to be converted to an open one with a midline infra-umbilical incision in order to protect the right appendages. A standard appendectomy was conducted, and the histology report revealed rupture of the appendix with concomitant wall inversion in the context of fibrous adhesions as well as obstruction due to a fecalith. Patient recovery and follow-up were excellent. Acute appendicitis, while frequently encountered in surgical practice, can present a diagnostic conundrum when it manifests in an atypical manner. This unique form of inversion appeared to confer a protective role against peritonitis, primarily through the mechanism of obstruction occurring centrally to the rupture. We suggest that this case should be included in current classifications as a partial inversion of the appendix after rupture and inflammation.

BACKGROUND: Chromosomal aberrations are as common as 13.8% in the infertile population. The incidence of pericentric inversion of chromosome 9 is approximately 1-3%. However, although these inversions do not alternate phenotype, there have been conflicting data about their effect as they were correlated with infertility, recurrent pregnancy loss, and deceased children, with no clear evidence of the inversions being the causative factor for these events.
METHODS: We report a case report of an Arab family with many members with inv(9)(p22q13). Our proband male aged 35 years at time of presentation with primary infertility. Some members, such as a brother aged 34 years, who had this inversion suffered from recurrent pregnancy loss while other members of similar reproductive age did not.
CONCLUSIONS: inv(9)(p22q13) might be a hereditary anomaly that might be a risk factor for recurrent pregnancy loss in its members.

Appendiceal inversion is a rare entity that can potentially mimic serious pathology and provide diagnostic uncertainty. They are mostly diagnosed intraoperatively or during endoscopies and scans for other reasons. We report a case of an asymptomatic patient treated for colon cancer without previous history of appendectomy. We provide long-term follow-up and aim to review the relevant literature.

Nail-patella syndrome (NPS, OMIM #161200) is a rare autosomal dominant disorder with symptoms from many different parts of the body, including nails, knees, elbows, pelvis, kidneys and eyes. It is caused by truncating variants in the LMX1B gene, which encodes a transcription factor with important roles during embryonic development, including dorsoventral patterning of the limbs. To our knowledge, inversions disrupting the LMX1B gene have not been reported. Here, we report a family with an inversion disrupting the LMX1B gene in five affected family members with mild but variable clinical features of NPS. Our finding demonstrates that genomic rearrangements must be considered a possible cause of NPS.

Supergenes offer spectacular examples of long-term balancing selection in nature, but their origin and maintenance remain a mystery. Reduced recombination between arrangements, a critical aspect of many supergenes, protects adaptive multi-trait phenotypes but can lead to mutation accumulation. Mutation accumulation can stabilize the system through the emergence of associative overdominance (AOD), destabilize the system, or lead to new evolutionary outcomes. One outcome is the formation of maladaptive balanced lethal systems, where only heterozygotes remain viable and reproduce. We investigated the conditions under which these different outcomes occur, assuming a scenario of introgression after divergence. We found that AOD aided the invasion of a new supergene arrangement and the establishment of a polymorphism. However, this polymorphism was easily destabilized by further mutation accumulation, which was often asymmetric, disrupting the quasi-equilibrium state. Mechanisms that accelerated degeneration tended to amplify asymmetric mutation accumulation between the supergene arrangements and vice-versa. As the evolution of balanced lethal systems requires symmetric degeneration of both arrangements, this leaves only restricted conditions for their evolution, namely small population sizes and low rates of gene conversion. The dichotomy between the persistence of polymorphism and degeneration of supergene arrangements likely underlies the rarity of balanced lethal systems in nature. This article is part of the theme issue \'Genomic architecture of supergenes: causes and evolutionary consequences\'.

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45-90% of affected individuals with DOA harbor pathogenic variants in the OPA1 gene. The mutation spectrum of OPA1 comprises nonsense, canonical and non-canonical splice site, frameshift and missense as well as copy number variants, but intragenic inversions have not been reported so far.
We report a 33-year-old male with characteristic clinical features of DOA. Whole-genome sequencing identified a structural variant of 2.4 kb comprising an inversion of 937 bp at the OPA1 locus. Fine mapping of the breakpoints to single nucleotide level revealed that the structural variation was an inversion flanked by two deletions. As this rearrangement inverts the entire first exon of OPA1, it was classified as likely pathogenic.
We report the first DOA case harboring an inversion in the OPA1 gene. Our study demonstrates that copy-neutral genomic rearrangements have to be considered as a possible cause of disease in DOA cases.

Nonpuerperal uterine inversion is a very rare event. We reported on the first ever case of nonpuerperal uterine inversion due to adenomyosis. Magnetic resonance imaging is recommended in cases with an unusual vaginal mass, so that this possible uterine etiology can be taken into consideration.

BACKGROUND: Clinical outcome after successful reorientation of an upside-down implanted DMEK (Descemet Membrane Endothelial Keratoplasty) graft 4 weeks after initial transplantation.
METHODS: A 71-year-old woman presented with Fuchs\' endothelial corneal dystrophy for DMEK. After initial DMEK the donor graft was fully attached and well centred during intracameral gas filling. When the gas bubble was fully resorbed the graft started to detach. Therefore, two intracameral gas injections were consecutively performed. During the second re-bubbling, an upside-down orientation was observed and so the graft was flipped, centred, re-attached and finally stabilized by an intracameral gas bubble. Three weeks after reorientation slit lamp examinations showed a well centred and attached graft, endothelial cells that started functioning and a patient\'s visual acuity of 20/40. Visual acuity increased to a 20/32 vision in the observed eye three months later and further improved to 20/20 6 months after reorientation and stayed stable between 20/32 and 20/20 during the remaining 15 months of follow-up, with a clear and well-attached graft.
CONCLUSIONS: Reorientation of an upside down DMEK graft was successful even 4 weeks after initial DMEK. Visual recovery and endothelial cell count increase were stepwise noticed during the first 6 months and 15 months after reorientation, respectively. Finally a favourable outcome with 20/32 to 20/20 vision at least 6 months after graft reorientation was achieved. Therefore, restoring full graft function could last several weeks or even months following (late) reorientation of an upside-down DMEK graft.